Unruptured Cohort Research Articles

Outcome study of the Pipeline Vantage Embolization Device (second version) in unruptured (and ruptured) aneurysms (PEDVU(R) study)

BackgroundThe Pipeline Vantage Embolization Device (PEDV) is the fourth-generation pipeline flow diverter for intracranial aneurysm treatment. There are no outcome studies for the second PEDV version. We aimed to evaluate...

694 Morphological Differences of Ruptured Versus Unruptured Wide Neck Aneurysms: Insights From the EVERRUN Registry

INTRODUCTION: Wide neck aneurysms (WNAs) have been defined as having a neck width >4 mm (N > 4) and/or dome-to-neck ratio <2 (DTNR < 2). Despite literature detailing treatment options for WNAs, there has been less study on the natural history of WNAs. METHODS: Ruptured and unruptured, saccular, not previously treated WNAs (N > 4, DTNR < 2, or both) were included. Differences in WNA morphology and patient demographics were compared between ruptured (R) and unruptured (U) cohorts. Statistical significance set at p < 0.05. All analysis performed using R(v.4.2.1). RESULTS: There were 310 WNA (87 R vs. 223 U). There were more females in both groups (R: 80.5%, U: 75.8%). Ruptured WNA were smaller (neck size R: 3.72 ± 1.39 mm, U: 4.5 ± 1.78 mm; dome width R: 5.04 ± 2.39 mm, U: 6.29 ± 3.37 mm, p < 0.05) with a trend towards reduced height (R: 5.04 ± 2.16 mm, U: 5.74 ± 3.01 mm) (p = 0.05). Ruptured aneurysms had higher rates of DTNR<2 alone (R: 60.9%, U: 42.2%) and unruptured aneurysms had higher rates of combined DTNR <2 and N >4 (R: 34.5%, U: 50.7%, p < 0.05). N > 4 alone was more prevalent in the unruptured cohort (R: 4.6%, U: 7.2%). ICA-Pcomm location (R: 21.1%, U: 9.4%) and AComm (R: 24.1%, U: 15.2%) were more common in the ruptured cohort. ICA-Oph location was more common in the unruptured cohort (R: 2.3%, U: 17.0%) (p < 0.05). Higher percentages of Asian (A), African American (AA), and Hispanic (H) patients were in the ruptured cohort compared to Caucasian (C) patients (A, R: 6.9%, U:0.9%; AA, R: 12.6%, U: 7.2%; H,R: 35.5%, U: 29.6%; C,R: 42.5%,U: 60.1%) (p < 0.05). CONCLUSIONS: Ruptured WNAs tend to be smaller with unfavorable DTNR whereas unruptured WNAs tend to be larger with a favorable DTNR. Higher rates of Pcomm/Acomm location in ruptured WNA are consistent with previous studies of all aneurysms. The significant racial disparity in ruptured vs. unruptured WNAs highlights the need to examine the biological and societal risks underlying these results.

693 Treatment Differences of Ruptured Versus Unruptured Wide Neck Aneurysms: Insights From the EVERRUN Registry

INTRODUCTION: Wide neck aneurysms (WNAs) are more challenging to treat compared to narrow neck aneurysms, requiring more advanced techniques. The Wide Neck / EVERRUN Registry compared endovascular versus microsurgical techniques for unruptured and ruptured aneurysms. METHODS: Saccular and not previously treated WNA were examined. WNA definition was aneurysm neck=4mm or dome-to-neck-ratio (DTNR)<2. Differences in treatment strategy (EVT vs. MS) and angiographic results were the primary outcomes. Angiographic outcome was assessed immediately following treatment and at last follow-up using the Raymond-Roy scale (core lab review, adequate occlusion: RR 1-2). Statistical significance set at p<0.05. All analysis performed using R(v.4.2.1). RESULTS: 310 WNA were included (87 ruptured (R) aneurysms vs. 223 unruptured (U)). There were no significant differences in the rate of EVT vs. MS between ruptured (R) vs. unruptured (U) aneurysms (Clipping, R: 36.8%, U: 37.7%). Amongst EVT, ruptured WNA were treated more with stand-alone coiling (R: 27.6%, U: 5.8%) and balloon-assisted coiling (R: 32.2%, U: 10.8%). Unruptured aneurysms were more commonly treated with flow diversion (R: 1.1%, U: 22.9%) and stent-assisted coiling (R: 2.3%, U: 21.5%) (p < 0.05 for all). Ruptured aneurysms had higher rates of adequate angiographic occlusion after initial treatment (R: 88.5%, U: 74.3%) (p < 0.05). There was no difference in final adequate occlusion at follow-up (R: 90.1%, U: 90.7%). Ruptured WNA had higher retreatment rates (R: 14.3%, U: 3.1%) (p < 0.05). Ruptured WNA had more procedural complications (R: 28.7%, U: 17%) (p < 0.05). Rates of good mRS (0-2) at one year were higher in unruptured WNA patients (R: 72.8%, U: 90.3%) (p < 0.05). CONCLUSIONS: WNA rupture status significantly influences the EVT choice, likely based on the need for DAPT. The lower initial adequate occlusion in the unruptured cohort is likely due to more flow diverter use. Ruptured WNAs were more difficult to treat as evidenced by higher rates of retreatment and procedural complications, however this did not impact the final angiographic outcomes.

Stereotactic Radiosurgery With vs. Without Prior Embolization for Brain Arteriovenous Malformations: A Propensity Score Matching Analysis

Objective: Whether partial embolization could facilitate the post-stereotactic radiosurgery (SRS) obliteration for brain arteriovenous malformations (bAVMs) remains controversial. We performed this study to compare the outcomes of SRS with and without prior embolization for bAVMs.Methods: We retrospectively reviewed the Beijing Tiantan AVMs prospective registration research database from September 2011 to October 2014. Patients were categorized into two groups, combined upfront embolization and SRS (Em+SRS group) and SRS alone (SRS group), and we performed a propensity score matching analysis based on pre-embolization baseline characteristics; the matched groups each comprised 76 patients.Results: The obliteration rate was similar between SRS and Em+SRS (44.7 vs. 31.6%; OR, 1.754; 95% CI, 0.905–3.401; p = 0.096). However, the SRS group was superior to the Em+SRS group in terms of cumulative obliteration rate at a follow-up of 5 years (HR,1.778; 95% CI, 1.017–3.110; p = 0.033). The secondary outcomes, including functional state, post-SRS hemorrhage, all-cause mortality, and edema or cyst formation were similar between the matched cohorts. In the ruptured subgroup, the SRS group could achieve higher obliteration rate than Em+SRS group (56.5 vs. 31.9%; OR, 2.773; 95% CI, 1.190–6.464; p = 0.018). The cumulative obliteration rate at 5 years was also higher in the SRS group (64.5 vs. 41.3%; HR, 2.012; 95% CI, 1.037–3.903; p = 0.038), and the secondary outcomes were also similar between the matched cohorts.Conclusion: Although there was no significant difference in the overall obliteration rate between the two strategies, this study suggested that pre-SRS embolization may have a negative effect on post-SRS obliteration. Furthermore, the obliteration rates of the SRS only strategy was significantly higher than that of the Em+SRS strategy in the ruptured cohort, while no such phenomenon was found in the unruptured cohort.

Periprocedural safety of saccular aneurysm embolization with the Penumbra SMART Coil System: a SMART registry subset analysis

BackgroundUsing data from the SMART registry, we report on periprocedural safety of the Penumbra SMART Coil System for endovascular coil embolization of saccular intracranial aneurysms.MethodsThe SMART registry was a prospective,...

Long-term outcomes of brainstem arteriovenous malformations after different management modalities: a single-centre experience

ObjectiveThe aims of this study are to clarify the long-term outcomes of brainstem arteriovenous malformations (AVMs) after different management modalities.MethodsThe authors retrospectively reviewed 61 brainstem AVMs in their institution between...

Make Clipping Great Again: Microsurgery for Cerebral Aneurysms by Dual-Trained Neurosurgeons

Despite an increasing focus on endovascular treatment of cerebral aneurysms, microsurgical clipping remains an integral part of management. We evaluated the safety and effectiveness of microsurgical clipping performed by dual-trained neurosurgeons at our institute, which has adopted an endovascular first approach. We retrospectively reviewed clinical and radiographic data of 412 aneurysms in 375 patients treated with microsurgical clipping. Univariate and multivariate analyses were performed to identify predictive outcome factors. We defined favorable outcome as a modified Rankin Scale (mRS) score of 0-2 at last clinical follow-up; unfavorable outcome was an mRS score of 3-6. We compared outcomes in our series with those of seminal aneurysm clipping series. Clipping of 330 of 351 unruptured aneurysms (94.01%) was associated with favorable outcome during the follow-up period (mean, 26.5 months). On univariate analysis, older patient age, intraoperative rupture, and higher baseline mRS scores were associated with unfavorable outcome in the unruptured cohort. On multivariate analysis, older age, higher baseline mRS scores, and posterior circulation aneurysm location were predictive of unfavorable outcome. Clipping of 46 of 61 ruptured aneurysms (75.4%) was associated with favorable outcome during the follow-up period (mean, 23.1 months). On univariate analysis, left-sided aneurysms, intraoperative rupture, and large aneurysm size were associated with unfavorable outcome in the ruptured cohort. On multivariate analysis, female sex was predictive of unfavorable outcome. Our ruptured and unruptured cohort results compared favorably with those in seminal series. Treatment by neurosurgeons adept at both endovascular and microsurgical techniques may improve clinical outcomes.

Clip-first policy versus coil-first policy for the exclusion of middle cerebral artery aneurysms.

Middle cerebral artery (MCA) aneurysms are a particular subset of intracranial aneurysms that can be excluded by clipping or coiling. A comparison of the results between these two methods is often limited by a selection bias in which wide-neck and large aneurysms are frequently treated with surgery. Here, the authors report the results of two centers using opposing policies in the management of MCA aneurysms: one center used a clip-first policy while the other used a coil-first policy, which limited the selection bias and ensured a good comparison of these two treatment modalities. All patients treated for either ruptured or unruptured MCA aneurysms at one of two institutions between January 2012 and December 2015 were eligible for inclusion in this study. At one center a clip-first policy was applied, whereas the other applied a coil-first policy. The authors retrospectively reviewed the medical records of these patients and compared their clinical and radiological outcomes. A total of 187 aneurysms were treated during the inclusion period; 88 aneurysms were treated by coiling and 99 aneurysms by clipping. The baseline patient and radiological characteristics were similar between the two groups, but the clinical presentation of the ruptured aneurysm cohort differed slightly. In the ruptured cohort (n = 90), although patients in the coiling group had a higher rate of additional surgery, the complication rate, functional outcome, and risk of death were similar between the two treatment groups. In the unruptured cohort (n = 97), the complication rate, functional outcome, and risk of death were also similar between the two treatment groups, although the risk of discomfort related to the temporal muscle atrophy was higher in the surgical group. Overall, the rate of complete occlusion was higher in the clipping group (84.2%) than in the coiling group (31%), which led to a higher risk in the coiling group of aneurysm retreatment within the first 2 years (p = 0.04). Clipping and coiling for MCA aneurysm treatment provide the same clinical outcome for ruptured and unruptured aneurysms. However, clipping provides higher short- and long-term rates of complete exclusion, which in turn decreases the risk of aneurysm retreatment. Whether this lower occlusion rate can have a clinical impact in the long-term must be further evaluated.

Abstract WP436: Comparing Risk of Stroke and Death in Treated and Untreated Patients With Unruptured Brain Arteriovenous Malformations (BAVM)

Background: Management of unruptured BAVM remains controversial despite recent clinical trial results demonstrating a 3-fold increased risk of stroke and death in treated versus medically managed patients. We compared outcomes between treated and untreated patients with unruptured BAVMs using observational data from the Multicenter AVM Research Study (MARS). Methods: MARS consists of 3 unruptured cohorts: UCSF (n=416), Columbia (n=223), and the Scottish Audit of Intracranial Vascular Malformations (n=70). We used a propensity score adjusted analysis with Cox proportional hazards regression of time to adverse event (stroke or death) from date of diagnosis or treatment, censoring at last follow-up (up to 5 years) to compare the group receiving any interventional treatment of embolization, gamma knife, or surgical resection (‘treated’) to the group receiving medical management (‘untreated’). The propensity score for treatment was computed using logistic regression with predictors of age, age2, sex, Caucasian race, cohort, Spetzler-Martin score, and reason for presentation. Results: There were 709 unruptured BAVM patients (565 treated/144 untreated). A total of 81 adverse events (68 strokes/13 deaths) occurred during 1632 patient-years of follow-up for an annual rate of 5.0% (95% CI: 4.0%-6.2%) overall, 5.6% (4.4%-7.2%) in the treated group, and 4.6% (2.0%-5.4%) in the untreated group. There was a trend for increased risk of adverse events in the treated group (HR=1.5, 95% CI:0.8-2.7, p=0.180). In stratified analysis, subjects in the highest propensity quintile (i.e., those most expected to receive treatment) seemed to have lower rates of adverse events in the treated versus untreated group (HR=0.4, 95% CI:0.1-1.5, p=0.178). An analysis using all patients except those in the highest quintile suggested outcomes were worse in the treated group (HR=1.81, 95% CI:0.96-3.4, p=0.065). Conclusion: Our results suggest an increased risk of adverse events in unruptured BAVMs that are treated. However, taking into account propensity for treatment revealed a possible subgroup that may benefit from treatment. Larger sample sizes are needed to identify risk factors and develop risk stratification models for unruptured BAVMs.

The Diagnosis and Management of Brain Arteriovenous Malformations in a Single Regional Center

Cerebral arteriovenous malformations are vascular abnormalities in which arteriovenous shunting occurs through an abnormal vascular network (nidus) in the parenchyma. These lesions typically present by the third decade of life with cerebral bleeding, seizures, headache, or neurologic deficits; however, they are sometimes found incidentally. A retrospective analysis of intracranial AVMs referred to a single regional center, over a 7-year period, was performed to review the clinical presentation, pathologic features and management outcomes from January 2005 to December 2012. We identified 142 patients (56% female, age range 4-69 years). Emergency referrals accounted for 87% of the cohort with the most frequent presentation being headache and/or hemorrhage. More than half (52%) of the cases were observed to have a neurologic deficit on examination. The modal Spetzler-Martin Grade was 3 with 76% of lesions located in areas of eloquent brain and 57% of cases in the dominant hemisphere. Half of the cases had multiple feeder vessels, and 29% were associated with aneurysms. The nidus was obliterated in 91% of cases actively managed. Two thirds of patients were successfully treated with a single modality, the most common being embolization. Only 8% of cases were managed conservatively. Additionally, 93% of aneurysms identified were treated successfully. The complication rate was 7% with 2% of reported infection. The burden of AVM management is significantly enhanced by the number of emergency referrals. Interestingly, complication rates are higher in the unruptured cohort. Surgical management is the most effective modality, but it carries the highest complication rate. This accompanied by the challenges of AVM anatomy and associated pathology argue for expert service provision in a single center.

Editorial: Aneurysm geometry

Treatment of small, unruptured intracranial aneurysms is controversial, and the decision of whether to intervene is a difficult one. While a very small subset of unruptured aneurysms go on to rupture, the vast majority remain quiescent for years. Different factors (related to patient, aneurysm, and surgeon/technique) are taken into consideration to guide the decision-making process. The development of 3D imaging techniques has triggered an expanding number of reports on the predictive role of various geometric and hemodynamic measurements on the formation, growth, and rupture of intracranial aneurysms. While estimation of the putative role of these measurements is appealing and sophisticated, most of the studies suffer from a major methodological flaw: unruptured aneurysms are compared with ruptured aneurysms. As most surgeons who have operated on patients with ruptured and unruptured aneurysms are well aware, the 2 entities are often completely different. In their article, Lin and coworkers1 analyze a relatively large cohort of middle cerebral artery (MCA) aneurysms and compare unruptured and ruptured aneurysms with respect to various geometric measurements calculated on 3D CT angiography reconstructions. The authors conclude that aspect ratio, flow angle, and parentdaughter angle were more common in the ruptured rather than in the unruptured cohort. The authors of this study make an attempt to consider a homogeneous group of aneurysms by selecting only patients with MCA aneurysms. However, the 2 groups under consideration are still quite different, and the study is not devoid of the significant methodological flaws of similar studies. I suspect that composition and strength of the aneurysm wall and time elapsed from aneurysm formation to its detection are much more important differences between ruptured and unruptured aneurysms than are geometric differences. Most aneurysms that go on to rupture most likely do so shortly after their formation at a time when the aneurysm wall is more vulnerable to hemodynamic stress.2,3 It is possible that aneurysm geometry plays a role in this early stage of vulnerability, hence the differences between ruptured and unruptured aneurysms. While the growing body of literature on fluid dynamics and aneurysm geometry has had important repercussions in designing newer treatments for intracranial aneurysms (such as flow diverters), the ever-increasing list of complex geometric factors associated with “rupture” has done little to change our decision making in patients with unruptured aneurysms or our understanding of the formation, growth, and rupture of intracranial aneurysms. A prospective study of conservatively treated unruptured aneurysms with analysis of geometric factors associated with rupture risk may provide useful information, but even such a study could be inconclusive because of the small number of end points (that is, ruptures) and the interaction with other important variables (aneurysm size, patient age, aneurysm location, and correctable risk factors for aneurysm rupture). Despite the growing body of literature on aneurysm/parent artery geometry and computational fluid analysis, the decision making in treating unruptured intracranial aneurysms continues to be based on art rather than science. (http://thejns.org/doi/abs/10.3171/2012.3.JNS112260)

The combined approach to intracranial aneurysm treatment

Background A consecutive series of patients with intracranial aneurysms in the practice of one neurovascular surgeon was retrospectively reviewed to illustrate that one physician can become proficient in microneurosurgery as well as endovascular surgery and achieve favorable outcomes in both disciplines. This supports one model of training for cerebrovascular surgeons that includes the complimentary practice of open microneurovascular surgery with endovascular surgery. Methods The senior author (HAR) treated 351 patients with 413 aneurysms between July 2001 and March 2007. Of these, 172 patients (216 aneurysms) were treated with open microneurosurgical techniques and 179 patients (197 aneurysms) were treated using endovascular techniques. Results Complete obliteration was attained in 94.3% of clipped aneurysms, and 61.9% and 65.9% of coiled aneurysms immediately and after at least 6 months of follow-up, respectively. At latest evaluation, 93% of endovascular patients and 90% of microneurosurgical patients had good clinical outcomes (GOS, 4 or 5; mean follow-up, 23 months; combines ruptured and unruptured cohorts). Procedure-related mortality included 1 surgical patient and 2 endovascular patients. Conclusions Because the fields of microvascular and endovascular surgeries are both technically complex, there has been concern that hybrid cerebrovascular surgeons cannot perform each technique with the skill necessary to achieve good outcomes. When compared to clipping and coiling reviews in the neurosurgical literature, we illustrate that one hybrid neurovascular surgeon is capable of attaining great facility in both techniques and that this type of physician will represent one practice model of cerebrovascular specialist in the future. This has potential implications for the training of hybrid cerebrovascular surgeons.

Invasive treatment of unruptured brain arteriovenous malformations is experimental therapy

Brain arteriovenous malformations (AVMs) are currently being treated in a variety of ways, including medical management, endovascular procedures, neurosurgery and radiotherapy. The widespread diffusion of these various treatment approaches is partially driven by the existence of variations in the perception about the risks of rupture, and how devastating such events would be. Data from the most recent studies suggest the majority of AVM patients are diagnosed without signs of hemorrhage, further, that the natural history risk for the unruptured cohort is far more benign than for those presenting with rupture. In cases where hemorrhage occurs, the clinical syndrome is significantly less disabling than in patients with non-AVM related hemorrhage. For unruptured AVMs, current morbidity data suggest a higher risk for invasive management than for the natural history of untreated patients. No randomized clinical trial data exist on the benefit of invasive AVM treatment, and the most contentious issue at present is whether intervention should be considered for AVMs that have not bled. In a scientific sense, invasive treatment for unruptured brain AVMs may be considered experimental therapy awaiting the results from 'A Randomized Trial of Unruptured Brain AVMs' (ARUBA), which is currently underway.